| CAS NO: | 1382979-44-3 |
| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 1mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| Storage | Store at -20°C |
| M.Wt | 382.42 |
| Cas No. | 1382979-44-3 |
| Formula | C18H22N8O2 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥2.83 mg/mL in DMSO with ultrasonic |
| Chemical Name | 5-(6,6-dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine |
| Canonical SMILES | NC1=NC=C(C2=NC(N3CCOCC3)=C4N=C5C(C)(C)OCCN5C4=N2)C=N1 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
GDC-0084 is a potent and brain penetrant inhibitor of PI3K and mTOR with Ki values of 2 nM and 70 nM for PI3Kα and mTOR, respectively [1].
Glioblastoma (GBM) is the most common primary brain tumor in adults and aberrant PI3K signaling is associated with more than 80% of cases. The PI3K pathway represents a potential target for the treatment of this disease and the inhibitors would need to freely cross the blood-brain barrier (BBB) [1][2].
GDC-0084 is a potent and brain penetrant inhibitor of PI3K and mTOR. In vitro kinase assay, GDC-0084 exhibited Ki values of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. In five different GBM cell lines, GDC-0084 had antiproliferative activities with EC50 values ranging from 0.3 to 1.1 μM. GDC-0084 has excellent human metabolic stability in microsomal and hepatocyte incubations [1]. In transfected cell lines over-expressing human or mouse P-gp or BCRP, GDC-0084 was a poor substrate of these efflux transporters. In mice brain, GDC-0084 significantly lowered pAkt and pS6 levels [2].
In rats after a 15 mg/kg dose of GDC-0084, the total brain-to-plasma ratio was 1.9-3.3. In subcutaneous U87 glioblastoma tumor xenograft mice model, GDC-0084 significantly inhibited tumor growth in a dose-dependent way. GDC-0084 also concentration-dependently inhibited pAKT [1].
References:
[1]. Heffron TP1, Ndubaku CO1, Salphati L1, et al. Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR. ACS Med Chem Lett. 2016 Feb 16;7(4):351-6.
[2]. Salphati L, Alicke B, Heffron TP, et al. Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma. Drug Metab Dispos. 2016 Dec;44(12):1881-1889. Epub 2016 Sep 16.
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